Why is this post inappropriate?

So: "These results support the potential of creating a quick, accurate and widely accessible method for differentiating risks between ASD [autism spectrum disorder] and ADHD [attention-deficit hyperactivity disorder]."That was a conclusion reached in the paper by Marlena Duda and colleagues [1] (open-access) building on their previous foray into this important research area (see here). Last time around [2] this research group - the Duda/Wall et al research combination - set the scene for boiling down the Social Responsiveness Scale (SRS) from 65 items to something considerably smaller when it came to distinguishing autism from ADHD. This based on the idea that autism and ADHD are not unstrange diagnostic bedfellows (see here).This time around, researchers set out to "expand upon our prior work by including a novel crowdsourced data set of responses to our predefined top 15 SRS-derived questions from parents of children with ASD (n=248) or ADHD (n=174) to improve our model’s capability to generalize to new, ‘real-world’ data." Mention of the term 'crowdsourced' means that authors utilised various online social media platforms to "to inform the community of the study" and gather responses. Importantly, they note that "diagnoses of ASD or ADHD were provided as parent report."Results: once again applying various machine learning algorithms to their recently captured data and "mixing these novel survey data with our initial archival sample (n=3417)" authors reported some interesting findings. Taking the two samples - the archival samples and the recent crowdsourced data - together they reported on the creation of "a classification algorithm that can generalize well to unseen data (AUC=0.89±0.01), even when those data have more natural variablity like the kind seen in our survey sample." This was based on the use of 15 items from the SRS.But... things were not all smooth sailing in this latest research effort. Bearing in mind the use of those 'parent reported' autism and ADHD participants in this latest study, authors noted that 'real-world' data is not necessarily the same as the very clinical data relied upon on the last research occasion. So: "In the archival sample, the responses for ADHD subjects were more uniform and on average less severe than the ADHD responses in the survey sample."Still, these are important results albeit requiring 'continued evaluation' as further crowdsourced and other data filter through. Indeed 'adaption' to new data seems to be something that the authors are particularly keen on to "further improve the generalizability of the classifier." I continue to applaud their research in this area as a function of their efforts (see here) to make autism and/or ADHD screening quicker, easier and more cost-effective.And on that last point. it is timely that such research continues given what is being proposed in certain parts of England when it comes to autism diagnoses (see here). Indeed, the suggestion of "restricting an autism diagnosis to only the most severe cases" as a function of some quite spectacular increasing demand - "The team is supposed to carry out 750 assessments a year. But it is getting almost double that level of demand, with about 25 referrals a week" - reiterates a need to streamline diagnostic services to make screening/diagnosis quicker, easier and more cost-effective.For those also who have said 'so what' to the increase in cases of autism (yes, someone actually did albeit with caveats), such proposals to potentially restrict autism diagnoses, I would say, are a direct result of such a mindset to 're-think' autism. Although well meaning, if enough people talk about difference over disability for example, purse string holders in the NHS (National Health Service) were eventually bound to ask 'why diagnose?' and 'why offer services?' (services that can cost quite a lot and even for those with 'severe autism' are often not there). As other authors have eloquently argued (see here) and indeed, foretold, mixed in with the current economic situation being put forward all in the name of austerity, low-hanging NHS services fruit like autism screening/assessment were certain to be eventually targeted and the 'difference over disability' framing unfortunately provides ample ammunition for such proposals...----------[1] Duda M. et al. Crowdsourced validation of a machine-learning classification system for autism and ADHD. Transl Psychiatry. 2017 May 16;7(5):e1133.[2] Duda M. et al. Use of machine learning for behavioral distinction of autism and ADHD. Transl Psychiatry. 2016 Feb 9;6:e732.----------Duda M, Haber N, Daniels J, & Wall DP (2017). Crowdsourced validation of a machine-learning classification system for autism and ADHD. Translational psychiatry, 7 (5) PMID: 28509905... Read more »

Why is this post inappropriate?

"Black women from East Africa had more than 3.5 times the odds of autism spectrum disorder with intellectual disability in their children than Caucasian nonimmigrant women."So said the study results reported by Jenny Fairthorn and colleagues [1] (open-access available here) providing yet more evidence for the need for much greater scrutiny as to why children of immigrant parents from East Africa are seemingly at higher risk of 'more severe' autism than other groups (see here and see here).Based on data from "Western Australian state registries" (yet again), researchers set about comparing autism prevalence with and without intellectual (learning) disability as a function of various variables: race (ethnicity), immigrant status and region of birth of mothers of children. The authors really drilled down into the details on immigrants according to their birth region in this study.Results: from a study sample of over 130,000 mothers, some 1000 had a child diagnosed with an autism spectrum disorder (ASD) together with intellectual disability (ID) and nearly 350 with a child with autism without ID. The figures equated to something like 0.7% of the total cohort with a child with autism and ID and 0.2% of the cohort with a child diagnosed with autism but not with ID. Authors also indicated that: "mothers of children with autism spectrum disorder with intellectual disability were more likely to be 40 years or more."Then to some important data: "After adjustment for demographic factors and compared to nonimmigrant women, immigrant women were less likely to have a child diagnosed with either autism spectrum disorder with intellectual disability or autism spectrum disorder without intellectual disability." This finding covered various geographic locations from which migrant mums came together with their race/ethnicity. That is however, aside from mothers from East Africa, and that "three-fold higher odds of having a child identified with autism spectrum disorder with intellectual disability." Authors added that "all autism spectrum disorder diagnoses in the children of Black mothers were of autism spectrum disorder with intellectual disability" and that all cases "were from mothers born in East Africa, with four born in Ethiopia and one each from Eritrea, Kenya, and Somalia."The authors acknowledge that their categorisations based on race/ethnicity and migration status led to some quite small group numbers being analysed (including not including any participants from other parts of Africa outside of East Africa). They also drew attention to the fact that their participant group of children with autism but without ID was quite a bit smaller than would be typically expected in comparison to the group with autism and ID (see here).But the results do paint an interesting picture and particularly with regards to those from East Africa, where they are in line with what has been previously discussed in the peer-reviewed and lay literature. The question of 'why' is probably going to be a complicated one as the authors suggested that "at least some of this difference could be the result of various factors leading to higher ascertainment of autism spectrum disorder in this group of children." They also qualify that statement by saying that they "cannot rule out the possibility of some biological risk factor, such as nutrition or stress" being involved which opens up a role for variables such as vitamin D exposure for example (see here).Personally, I think there are a few additional research directions that might need to be considered, primary among them is to have a little more detail on what autism prevalence might specifically look like in various areas of East Africa and Africa in general. I know this is a bit of a difficult ask in places where resources are really quite scarce, cultures are different (see here) and practical efforts for population screening are hindered by politics and the like. Until however we have such data, alongside some other important social and biological information, science doesn't have any 'baseline' measures on which to compare and contrast when it comes to families emigrating from such places and the possible reasons/changes that could be involved in this process and pertinent to offspring autism risk.----------[1] Fairthorne J. et al. Maternal Race-Ethnicity, Immigrant Status, Country of Birth, and the Odds of a Child With Autism. Child Neurol Open. 2017 Jan 12;4:2329048X16688125.----------Fairthorne J, de Klerk N, Leonard HM, Schieve LA, & Yeargin-Allsopp M (2017). Maternal Race-Ethnicity, Immigrant Status, Country of Birth, and the Odds of a Child With Autism. Child neurology open, 4 PMID: 28503625... Read more »

Why is this post inappropriate?

"Adults and children with CFS/ME [chronic fatigue syndrome / myalgic encephalomyelitis] have greater health care needs than the rest of the population for at least ten years before their diagnosis, and these higher levels of health care resource use continue for at least ten years after diagnosis."So concluded the study published by Simon Collin and colleagues [1] (open-access available here) who once again (see here) relied on data derived from the "Clinical Practice Research Datalink (CPRD) GP practices in the UK" to further explore aspects of the debilitating condition(s) headed under the banner of CFS/ME.Using a case-control design, researchers set out to "investigate long-term patterns in health care resource use before and after a diagnosis of CFS/ME." They had a hypothesis in mind before any study results were produced in that "health care resource use would increase from around the time of patient-reported onset of illness... until diagnosis" but "did not have a prior hypothesis about post-diagnosis health care resource use, although this might be expected to fall if diagnosis led to referral and effective treatment."Their results based on "916 child (age <18 years) and 6710 adult patients" suggested a few things: (i) "a steep drop in resource use immediately after diagnosis was followed by sustained higher levels of health care resource use for at least ten years after diagnosis", (ii) adults and children with CFS/ME tended to have greater healthcare resource use "for at least ten years before the diagnosis", and (iii) allied to that last point: "there were steep increases in use of health care resources 2–4 years before diagnosis in adults and 1–2 years before diagnosis in children." Healthcare resource use, by the way, was defined as including several things including: "GP [general practitioner] consultations, tests, prescriptions, and referrals" (with certain caveats).Although carrying an important message that elevated healthcare resource use is associated with a diagnosis of CFS/ME (bearing in mind the limitations of the CPRD when it comes to CFS/ME), one has to be quite careful with how facets of the Collin data are handled. I say this specifically on the basis that healthcare use 'at least ten years before diagnosis' was found to be elevated for those with CFS/ME and how authors talk about this conflicting with "patients reporting that they were fit and well prior to the onset of their illness." You can perhaps see how this data *could* be used by some to 'challenge' patients with reference to their reliability in reporting their illness onset for example and/or the idea that "behaviour traits such as disease conviction and somatic concern could not be discounted as aetiological factors." This in the context that the biopsychosocial model of CFS/ME is still prevalent in some quarters (see here) particularly those linked to healthcare interactions.Thankfully the authors offer a couple of other potentially important reasons to account for their results based on (a) "people may simply have had CFS/ME for a very long time" and/or (b) "it is possible that people who develop CFS/ME have pre-existing risk factors which lead to higher rates of health care resource use." Indeed, on that second point, one might even argue that specific pre-existing medical complaints could/would/might predispose someone to developing CFS/ME (see here) particularly with all the talk about immune function potentially being a facet of some CFS/ME for example (see here). In this context, we perhaps need to know a little more about the genetics potentially important to CFS/ME, bearing in mind the emerging theme that condition-specific genes are not just genes specific to any one condition (see here for example).Accepting also that authors were "unable to determine from our data whether the type of health care resource use by patients changes following diagnosis" the finding that healthcare use continues to be fairly high after diagnosis is a worrying sign. It suggests that modern medicine might not be particularly good at treating/managing those with CFS/ME (and their associated conditions) in the longer term based on current best practice. I could be a little bit cynical on this point in relation to how current 'best practice' for managing/treating CFS/ME involves some rather controversial techniques which could be construed as 'failing' in the context of these results. Indeed, I will refer you to a quote by Jonathan Edwards [2] talking about the on-going controversy in CFS/ME circles in relation to how current best practice might not be as successful as many might think: "If they are still ill, presumably these approaches have failed and the priority is to find something more effective." Indeed.----------[1] Collin SM. et al. Health care resource use by patients before and after a diagnosis of chronic fatigue syndrome (CFS/ME): a clinical practice research datalink study. BMC Fam Pract. 2017 May 5;18(1):60.[2] Edwards J. PACE team response shows a disregard for the principles of science. 2017. J Health Psychology. March 28.----------Collin, S., Bakken, I., Nazareth, I., Crawley, E., & White, P. (2017). Health care resource use by patients before and after a diagnosis of chronic fatigue syndrome (CFS/ME): a clinical practice research datalink study BMC Family Practice, 18 (1) DOI: 10.1186/s12875-017-0635-z... Read more »

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"Our study indicated that the use of ART [assisted reproductive technology] may [be] associated with higher risk of ASD [autism spectrum disorder] in the offspring. However, further prospective, large, and high-quality studies are still required."So said the results of the meta-analysis published by Liang Lui and colleagues [1] (open-access) surveying the peer-reviewed research literature - "11 records (3 cohort studies and 8 case-control studies)" - between 2006 and 2015. ART covers a variety of techniques "to achieve pregnancy and live birth" most notably including IVF (in vitro fertilisation) and artificial insemination. Some, but not all, of the studies included for review suggested an *association* between ART use and enhanced risk of offspring autism particularly in "European and Asian populations." The authors were however unable to tease apart which specific ART(s) might be associated with a higher risk than others.This is not the first time that this topic has been covered on this blog (see here). On that previous occasion I intimated that the source of any risk from ART on offspring autism was not yet identified and, in some cases, other birth factors might exert some effect. In short, it's more complicated than paper titles can transmit.Does my opinion change as a result of these meta-analysed findings? Well, not really. I appreciate the findings reported by Lui and colleagues but I still think other birth factors might come into play outside of just ART exerting a primary effect. Not least is the possibility that issues affecting fertility in the first place might be particularly relevant among other confounders. I echo the sentiments of the authors that more research might be required in this area but with the various stresses and strains being placed on autism research resources these days, I'm not inclined to suggest that this area should necessarily be top of this list of priorities. Sorry.----------[1] Liu L. et al. Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis. Sci Rep. 2017 Apr 7;7:46207.----------Liu L, Gao J, He X, Cai Y, Wang L, & Fan X (2017). Association between assisted reproductive technology and the risk of autism spectrum disorders in the offspring: a meta-analysis. Scientific reports, 7 PMID: 28387368... Read more »

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'Low dose' has been a feature of my autism research reading this week; first starting with the results from Dan Quintana and colleagues [1] talking about some important effects following intranasal delivery of low dose oxytocin and then moving on to the primary reason for this entry with results from Robert Naviaux and colleagues [2] (open-access) continuing a research theme looking at suramin and autism (see here for some background).For those interested in the oxytocin-autism research base, I can recommend following Dr Quintana on Twitter (find him here).In relation to the Naviaux findings - the "Suramin Autism Treatment-1 (SAT-1) trial" - well, they are open-access but I want to provide some overview and then a little bit of discussion. I might add that this research team are making research waves in several areas of medical science as per their research foray into chronic fatigue syndrome (CFS) recently (see here). Such 'metabolomic' research is pertinent to their autism research too.This time around as on previous research occasions, the focus was on suramin - the "century-old sleeping sickness drug" - and, as far as I can see, the first time said drug has been tested experimentally with children diagnosed with an autism spectrum disorder (ASD). The accompanying ClinicalTrials.gov trial entry is here.As per the title to this blog entry, this was a small trial including only 10 participants, all male, aged between 5-14 years old. This was a randomised-controlled trial (RCT) with a placebo element to it too, so half of the participants got suramin - "a single, intravenous infusion of suramin (20 mg/kg)" - and half got saline as a control. Alongside looking at behaviour and functioning, researchers also took blood and urine samples "for safety and toxicity monitoring at 5 times throughout the study." This was accompanied by quite a bit of effort to look at the possibility of adverse events related to suramin or placebo administration.Results: "A single intravenous dose of suramin was associated with improved scores for language, social interaction, and decreased restricted or repetitive behaviors measured by ADOS, ABC, ATEC, and CGI scores. None of these improvements occurred in the five children who received placebo." The authors also do the right thing by stating: "The generalizability of these findings is unknown." I'm particularly impressed that the ATEC gets a showing given the rise and rise of this autism research tool (see here) in various placebo-controlled contexts (see here).In relation to the safety aspect to suramin, well, it seemed to do alright. We are told that: "Extensive monitoring revealed no serious toxicities" so one can assume that the 'first, do no harm' tenet was upheld in this trial. But there was one important side-effect noted: "Five children who received suramin developed a self-limited, evanescent, asymptomatic, fine macular, patchy, morbilliform rash over 1–20% of their body." The rash was short-lived and did not require specific attention/intervention but it's worthwhile noting it especially when nothing similar was reported in the placebo group.Going back to the mention of this research group delving into CFS with metabolomics in mind, so similar results are reported on the basis of examination of plasma samples from participants. Various biological pathways seemed to be affected by the infusion of suramin, not least "the importance of the cell danger response (CDR) [3]... and purinergic signaling." Interestingly, authors also noted effects in relation to "1-carbon, folate, methionine, and cysteine metabolism" too, potentially linked to other findings independently reported in relation to autism (see here for example).Reiterating again that this was a small study (albeit using the gold-standard in scientific methodologies) these results are rather interesting and potentially quite important. They most definitely point to the requirement for further large-scale studies to look at any effects in a larger participant group and to 'zoom in' on potential best-responders to this type of intervention. I end with an important conclusion from the authors who again, have not over-stated their findings:"Suramin is not approved for the treatment of autism. Like many intravenous drugs, when administered improperly by untrained personnel, at the wrong dose and schedule, without careful measurement of drug levels and monitoring for toxicity, suramin can cause harm. Careful clinical trials will be needed over several years at several sites to learn how to use low-dose suramin safely in autism, and to identify drug–drug interactions and rare side effects that cannot currently be predicted. We strongly caution against the unauthorized use of suramin."----------[1] Quintana DS. et al. Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial. Transl Psychiatry. 2017 May 23;7(5):e1136.[2] Naviaux RK. et al. Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial. Annals of Clinical & Translational Neurology. 2017. 26 May.[3] Naviaux RK. Metabolic features of the cell danger response. Mitochondrion. 2014; 16: 7-17.----------Naviaux, R., Curtis, B., Li, K., Naviaux, J., Bright, A., Reiner, G., Westerfield, M., Goh, S., Alaynick, W., Wang, L., Capparelli, E., Adams, C., Sun, J., Jain, S., He, F., Arellano, D., Mash, L., Chukoskie, L., Lincoln, A., & Townsend, J. (2017). Low-dose suramin in autism spectrum disorder: a small, phase I/II, randomized clinical trial Annals of Clinical and Translational Neurology DOI: 10.1002/acn3.424... Read more »

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"Among patients with ADHD [attention-deficit hyperactivity disorder], rates of MVCs [motor vehicle crashes] were lower during periods when they received ADHD medication."That was the research bottom-line discussed by Zheng Chang and colleagues [1] who continue a theme on how managing/treating the symptoms of ADHD can often have some profound effects on those diagnosed with ADHD and also the wider population.The outcome measure on this occasion was MVCs; in particular: "Emergency department visits for MVCs" as assessed from data from the "Truven Health Analytics MarketScan Commercial Claims and Encounters databases." I've talked about the application of this resource in a research context before on this blog (see here). Such Emergency Room (ER) (also known as Accident & Emergency (A&E) here in Blighty) visits were assessed for those with and without a diagnosis of ADHD or those in receipt of "ADHD medication between January 1, 2005, and December 31, 2014." Authors compared the "risk of at least one MVC between patients with ADHD and matched controls."The results, based on quite a large number of people (2 million+) diagnosed with ADHD, suggested that: "Patients with ADHD had a significantly higher risk of an MVC than their matched controls." Medication for ADHD - of which over 80% of the cohort with ADHD were taking - seemed to affect the risk of MVCs as per the sentence introducing this post. Indeed authors noted: "months with ADHD medication were associated with a 12%... lower risk of MVCs in male patients with ADHD relative to unmedicated months and a 14%... lower risk of MVCs in female patients with ADHD." The figures actually got even better for risk reduction of MVCs when analysed at the "within-individual" level: "men with ADHD were 38% less likely to have MVC events during medicated months relative to unmedicated months" and for women, this figure went up to 42% less likely to have an MVC during medicated months. All-in-all, treating ADHD with medication meant less visits to the ER for motor vehicle crashes.Accepting that the use of medication for ADHD (or anything else) is not something that should ever be entered into lightly, there is quite a large body of evidence emerging suggesting that specific preparations at least, are both safe and reliable in terms of tackling the symptoms of ADHD (see here). Indeed, clinicians are seemingly becoming a lot more comfortable with employing pharmacotherapeutic strategies for ADHD (see here) probably in part, due to the effectiveness of available medications and their pretty good safety profile. I say all that noting that medication is not necessarily the only tool in the arsenal (see here and see here for examples).Of course there are caveats to this latest set of results; not least that this was a study looking at two variables (MVCs leading to ER attendance and ADHD medication(s)) and so might potentially have missed other data/factors (e.g. MVCs not requiring ER attendance). One also assumes that ADHD medication prescriptions were also being taken uniformly every day as indicated...Still, there is good reason to think that ADHD medication might be 'doing what it says on the tin' in terms of tackling issues such as inattention and impulsivity and how this had knock-on effects for MVCs requiring hospitalisation. Indeed, thinking also about the safety of other motorists who might have potentially benefited from the behaviour of those drivers with ADHD under medication, one can only see the life-changing potential of these informative results...----------[1] Chang Z. et al. Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder and Risk of Motor Vehicle Crashes. JAMA Psychiatry. 2017. May 10.----------Chang Z, Quinn PD, Hur K, Gibbons RD, Sjolander A, Larsson H, & D'Onofrio BM (2017). Association Between Medication Use for Attention-Deficit/Hyperactivity Disorder and Risk of Motor Vehicle Crashes. JAMA psychiatry PMID: 28492937... Read more »

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"Data showed that the children with ASD [autism spectrum disorder] had significantly (p < 0.001) higher levels of mercury and arsenic and a lower level of cadmium."And... "It is desirable to continue future research into the relationship between ASD and heavy metal exposure."Those sentences come from the study by Huamei Li and colleagues [1] continuing a research theme regarding (generally) elevated levels of heavy metals being detected in those on the autism spectrum (see here). Yes, I know that this kind of research is not always met with great appreciation (see here) but the suggestion that the heavy metal burden seems to be quite a bit higher in the autistic population is not something that can just be ignored. More so when it might actually be treatable (with no medical or clinical advice given or intended)...There are numerous other examples in the peer-reviewed science literature that I could give where the heavy metal burden has been found to be elevated in relation to autism. Indeed, if someone is looking for yet another systematic review and meta-analysis topic, there you go - you're welcome. Personally, I think we've reached the point where the questioning needs to move on to (a) the possible sources of those heavy metals and (b) whether 'exposure amount' is the sole reason for the elevations in relation to autism over and above issues with the biology around 'detoxifying' said metals. Answers are not likely to be simple but questioning has to continue...To close, he was always my favourite James Bond...----------[1] Li H. et al. Blood Mercury, Arsenic, Cadmium, and Lead in Children with Autism Spectrum Disorder. Biol Trace Elem Res. 2017 May 8.---------- Li H, Li H, Li Y, Liu Y, & Zhao Z (2017). Blood Mercury, Arsenic, Cadmium, and Lead in Children with Autism Spectrum Disorder. Biological trace element research PMID: 28480499... Read more »

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"Only irritable bowel syndrome (IBS) emerged as a risk factor for BD [bipolar disorder] supported by convincing evidence."So said the results of the umbrella review of systematic reviews and meta-analyses by Beatrice Bortolato and colleagues [1] looking at the various environmental risk factors potentially linked to the diagnosis of bipolar disorder. I might add that this is a topic that has been discussed before on this blog (see here and see here for examples).If the systematic review / meta-analysis represents the top of the research methodology hierarchy, a review including a number of systematic reviews and meta-analyses represents the cherry on top. Indeed, there is a growing trend of this kind of research (see here).The authorship names included on the Bortolato paper are not unfamiliar to this type of study methodology (see here) and specifically, the focus on psychiatric and somatic variables often being intertwined. This time around attentions turned to bipolar disorder, previously called manic depression, and a survey of 16 research publications identified listing over 50 "unique environmental risk factors for BD." The report of a possible link (with 'convincing evidence') between IBS and BD consolidates the idea of a gut-brain axis. Authors also detailed a few other factors as showing weaker but not necessarily less important connections to BD including childhood adversity, obesity and asthma. Focusing in on asthma in particular - a condition again previously talked about in the context of BD - I am wondering whether there are quite a few more generalisations connected to this diagnosis within the context of psychiatric labels (see here and see here)?Of course, more science is indicated on the hows-and-whys of connections such as the one between IBS and BD and the tantalising prospect of new intervention avenues if such a relationship is further confirmed. Minus any medical or clinical advice, I'm specifically thinking about how alterations to the gut microbiome accompanying cases of IBS might mean that talk of things like probiotics affecting the symptoms of IBS (see here) could be applicable to the presentation of [some] BD too. That and the idea that certain dietary elements might also be important to cases (see here and see here)...To close, I know that the past few days have not exactly been ones for smiling, but if some smiles and laughter are what you need, then the animal kingdom can provide them...----------[1] Bortolato B. et al. Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta-analyses. Bipolar Disord. 2017; 00: 1–13.----------Bortolato, B., Köhler, C., Evangelou, E., León-Caballero, J., Solmi, M., Stubbs, B., Belbasis, L., Pacchiarotti, I., Kessing, L., Berk, M., Vieta, E., & Carvalho, A. (2017). Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta-analyses Bipolar Disorders DOI: 10.1111/bdi.12490... Read more »

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I'm not usually so forthright with my posts on this blog, but today I'm being a little more bullish as I talk about an editorial from Simon Baron-Cohen [1] titled: "Neurodiversity – a revolutionary concept for autism and psychiatry."The crux of the SBC paper is the suggestion that use of the term 'disorder' specifically with autism in mind might have certain connotations - "Disorder should be used when there is nothing positive about the condition" - and until the "biomedical mechanistic cause of a disorder becomes known" some thought should go into the way autism for example, is described.The author seems to come down on something between 'difference' and 'disability' as being valid replacements, bearing in mind the wide - very wide - heterogeneity that is the autism spectrum and the fact that 'disorder' is still very prominent in the formal clinical descriptions of autism and related diagnoses (see here). Indeed on the topic of 'biomedical mechanistic causes' and [some] autism, well, there is already some evidence for this (see here)...Personally, I don't want to get involved in such disorder/difference debates. I say this on the basis that (a) people have their own ideas, descriptions and motivations for talking about what autism is and isn't to them (and who I am to question them and their views) and (b) from a research and clinical point of view, such linguistic differences make little difference when it comes to whether someone does or does not reach critical cut-off points for being on the autism spectrum and the subsequent help and support required. These are cultural issues not fundamental research or clinical ones (although I daresay some people would argue against that last point).What I do however want to mention about the Baron-Cohen article is that specific sentence described in the title of this post - "there is no single way for a brain to be normal" - in relation to neurodiversity [2] and how said phrase helps dismantle a problematic term present in various autism circles: neurotypical (NT).I see the word neurotypical (NT) banded about a lot these days including in the peer-reviewed domain. I assume from the name that the term describes 'others' who within the vast spectrum of diversity - neuro and otherwise - are, in relation to autism, not positioned on the autism spectrum. It's basically an 'us-and-them' term, which means not-autism (or other condition where similarly applied).The problem I have with this term relates to the questions: what exactly is neurotypical? and who actually falls under such a description?OK, we have the first bit - neuro - which is also used/misused a lot these days (together with some scepticism) I assume referring to the brain. Autism is often described in terms of the brain (structure, connectivity, 'wiring') as mentioned in the Baron-Cohen text, with some groups even talking about the possibility of an 'autistic brain' (see here). More precisely 'neuro' probably better describes the nervous system so one might instead look to the term 'autistic nervous system' as being more accurate (bearing in mind the brain is but one thinking organ in the body!). The second part - 'typical' - on it's own means just that: classic, quintessential, representative. Put them both together and the suggestion is that there is an 'average, representative brain / nervous system' in the population that is distinct from the 'autistic brain / nervous system'.Why is this problematic? Well, this is where the concept of 'identity' has I think perhaps overstretched itself.The 'autistic brain'? Bullshit (pardon my language). As I've said before on this blog, there is nothing in the peer-reviewed science literature to yet say that the brains / nervous system of everyone diagnosed as being on the autism spectrum are in any way universally different from those not reaching thresholds for the autism spectrum (see here). Nothing. Not one article. Indeed, with the greater recognition that autism is probably a plural condition covered by a singular label (see here), the likelihood that something / anything will universally define the 'autistic brain' is becoming even more distant. Y'know, much like the fading concept of an autistic gene that's taken so long to consign to the research dustbin/trashcan. I say all this even before we start to add-in the idea that autism rarely exists in some sort of diagnostic vacuum (see here) in these days of ESSENCE (see here).OK, you might say that 'typical' could be stretched to include a wider spectrum of brains / functioning / thinking rather than just one singular thing? Well, that's true but here's another issue: at what point does 'typical' then turn into 'atypical'? The inference is that alongside the neurotypical there is something akin to the neuroatypical. Where are these boundaries of neurotypical and neuroatypical? Do the boundaries shudder to an abrupt halt the moment cut-off points for a diagnosis of autism are reached or surpassed? Does this also mean that other labels such as attention-deficit hyperactivity disorder (ADHD) are also outside of the term neurotypical? Really? On what evidence?Then also there are the various observations that the presentation(s) of autism - the symptoms / characteristics / label - might actually be quite fluid across different people according to variables such as age or environment and how that further complicates the neurotypical concept. I've talked for example, before about how something like diagnostic stability is perhaps not as stable as many people might think when it comes to some autism (see here) and indeed, in relation to other over-represented comorbidity too (see here). Does this mean that those for example, currently not fulfilling the diagnostic criteria for autism but having previously done so at some previous point have somehow 'transitioned' from autism to neurotypical? Again, really? On what evidence?I could go on (and on) about the other problems with the concept of neurotypical (e.g. the problem of objectively measuring thinking styles, etc) but I won't. All I'll say is that in the age of 'show me the evidence' please do show me the evidence - any evidence - that neurotypical is anything other than an alternative phrase to 'not-autism' or at least not meeting the current cut-off thresholds for a diagnosis of autism or related label.And, on the basis of the points I've raised in today's post, how then can science continue to justify it's use when the description of neurotypical is, by all accounts, a nonsense?----------[1] Baron-Cohen S. Editorial Perspective: Neurodiversity - a revolutionary concept for autism and psychiatry. J Child Psychol Psychiatry. 2017 Jun;58(6):744-747.[2] Armstrong T. The myth of the normal brain: embracing neurodiversity. AMA J Ethics. 2015 Apr 1;17(4):348-52.----------... Read more »

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A quote to begin this post: "this preliminary study demonstrates that altered AGDA [antibodies against gliadin-derived antigen] levels in the circulation are associated with schizophrenia and could serve as biomarkers for the identification of a schizophrenia subgroup that may need an alternative therapy or precision treatment."So said the findings reported by McLean and colleagues [1] (open-access) looking at an area of some interest to this blog (see here) on how dietary gluten might show something of an important relationship to at least some cases of schizophrenia. Just in case you weren't aware, there is quite a history when it comes to gluten and schizophrenia (see here) as per the very forward-thinking of people such as Curt Dohan and Karl Reichelt.Researchers on this latest occasion set about looking in a little more detail at the suggestion that circulating anti-gliadin antibodies (AGAs) reflective of an immune response to a component of dietary gluten might show some connection to schizophrenia. Indeed they note that "all the tests for circulating AGAs in schizophrenia have been developed with mixtures of full-length native gliadins consisting of ~300 amino acid residues" suggesting that such a scatter gun approach may have included epitopes "that are unlikely to survive digestion in the gut." So, they instead "measured plasma levels of IgG and IgA against indigestible peptide fragments derived from γ- and α-gliadins" in archived plasma samples from "169 patients with schizophrenia and 236 control subjects."The results - based on the use of an "In-house ELISA for antibodies against gliadin-derived antigens" - were rather intriguing. So: "There was no significant difference in the levels of plasma antibodies against native gliadins between the patient group and the control group." If I'm reading this right, this finding is in contrast to other independent research occasions [2]. Indeed, when it came to looking at both IgA and IgG plasma anti-gliadin antibodies, there was no significant difference between the schizophrenia and non-schizophrenia participants as groups.But... when it came to a specific gliadin (γ-Gliadin) derived fragment - AAQ6C - with the amino acid sequence HPKCSIMRAPFASIVAGIGGQYRD - researchers reported on something potentially important to see: "patients with schizophrenia had significantly higher levels of plasma anti-AAQ6C IgG than control subjects." Importantly too, authors also noted that anti-psychotic medication did not appear to influence their antibody results. This was important given that seemingly all of the participants diagnosed with schizophrenia were taking one or more of this class of medicine. In line with the opening quote to this post, the authors make a preliminary foray into the possible 'biomarker' usefulness of the various anti-gluten antibodies for schizophrenia. I have to say on this point however, that the data is not that impressive as things currently stand.There is more to do when it comes to the possible effects of dietary elements containing gluten (and casein) in relation to cases of schizophrenia. This work adds something to the idea that diet can affect psychiatry/behaviour/development but what is perhaps missing is the recognition that schizophrenia is probably a heterogeneous and plural condition (see here and see here for examples) and as such, not every case is going to be gluten and/or casein-related. I do agree with the authors that more research is needed in this area alongside the idea that intervention via either dietary changes [3] and/or other options might also be on the research agenda...----------[1] McLean RT. et al. Differential antibody responses to gliadin-derived indigestible peptides in patients with schizophrenia. Translational Psychiatr. 2017. May 9.[2] Dickerson F. et al. Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry. 2010 Jul 1;68(1):100-4.[3] Jackson J. et al. A gluten-free diet in people with schizophrenia and anti-tissue transglutaminase or anti-gliadin antibodies. Schizophrenia Res. 2012;140(0):262-263.----------McLean RT, Wilson P, St Clair D, Mustard CJ, & Wei J (2017). Differential antibody responses to gliadin-derived indigestible peptides in patients with schizophrenia. Translational psychiatry, 7 (5) PMID: 28485731... Read more »

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Yet another 'continued' or 'part 2' short post for you today, building on some previous - very preliminary research - talking about the use of gastrin-releasing peptide (GRP) and autism (see here).The authors included on the paper by Josemar Marchezan and colleagues [1] are familiar ones to this part of the autism research landscape as per the other occasions that members of this group have looked at / talked about GRP and autism in the peer-reviewed domain.GRP is all about a compound that 'does what it says on the tin' insofar as stimulating the release of gastrin from specialist cells in the stomach. This in turn leads to the secretion of gastric acid among other things and onward aids the digestion of food.This time around Marchezan et al describe the results of a controlled trial on the use of GRP (vs. placebo) in a small group of boys (N=10) diagnosed with autism. This is a step-up from their previous research efforts in this area talking about a case series report and an open (non-blinded, non-placeboed?) study. Participants were given the same amount of GRP (160 pmol/kg) over the same number of days (4 consecutive days) as that detailed in their previous studies. This time around, the Aberrant Behavior Checklist (ABC) scale was the outcome measure of choice.Results: well, let's put it one way, they weren't exactly astounding in terms of any positive effects from the use of GRP over such a short space of time. This was exemplified by the authors use of "no statistical difference" when it came to looking at quite a lot of the data obtained during the investigation comparing GRP to placebo. On the plus side there were "no adverse effects, changes in vital signs, or laboratory abnormalities associated with the use of GRP" so the whole 'first do no harm' bit seems to be intact, at least in the short-term.Whilst it would be easy to sweep such results under the 'did not work' carpet, I am however minded to go with the authors' suggestion that "further research with other designs and a larger sample size to evaluate the efficacy and safety of GRP in children with autism" would be a step forward. I say this on the basis that hypochlorhydria - low levels of gastric acid - is not something completely unknown to parts of the autism spectrum (see here) and does suggest some *possible* involvement for something like GRP in specific cases of autism.----------[1] Marchezan J. et al. A Placebo-Controlled Crossover Trial of Gastrin-Releasing Peptide in Childhood Autism. Clin Neuropharmacol. 2017 Apr 27.----------Marchezan, J., Becker, M., Schwartsmann, G., Ohlweiler, L., Roesler, R., Renck, L., Gonçalves, M., Ranzan, J., & Riesgo, R. (2017). A Placebo-Controlled Crossover Trial of Gastrin-Releasing Peptide in Childhood Autism Clinical Neuropharmacology DOI: 10.1097/WNF.0000000000000213... Read more »

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Consider this short post a sort of follow-on to a previous entry on this blog concerning the elevated risk of injury following a diagnosis of attention-deficit hyperactivity disorder (ADHD). The paper in question today is that by Wu-Chien Chien and colleagues [1] who yet again [2], brought the quite significant scientific weight of the "National Health Insurance Research Database in Taiwan" to bear on this topic.In this latest paper, Chien et al relied on data from a 'subset' of the main insurance research database and found some not unexpected things: "The patients with ADHD had a 143% increased risk of overall injuries than the controls after considering all the confounding factors" and "the use of methylphenidate was associated with a 22.6% decrease in the risk of injuries in the patients with ADHD."What's more to say? Well, yet again risk of adverse issues *correlating* with a diagnosis of ADHD comes to the forefront (see here for another example). Yet again the idea that 'tackling' ADHD is a worthy goal (for many reasons) if not only to mitigate such elevated risks being presented, bearing in mind that medication "approved solely for ADHD treatment" is not some sort of magic bullet [3]. There are also other potentially important intervention options to look at (see here for example). I'm minded at this point to also bring in the recent findings reported by Borschuk and colleagues [4] talking about how comorbid asthma accompanying ADHD (yes, there is a surprisingly strong relationship between the two diagnoses) might play a role in the expression of ADHD and onwards provide some 'interesting' directions when it comes to tackling ADHD and it's elevated risk for various adverse outcomes...To close, appreciating a talent...----------[1] Chien WC. et al. The risk of injury in adults with attention-deficit hyperactivity disorder: A nationwide, matched-cohort, population-based study in Taiwan. Res Dev Disabil. 2017 Apr 27;65:57-73.[2] Kang JH. et al. Attention-deficit/hyperactivity disorder increased the risk of injury: a population-based follow-up study. Acta Paediatr. 2013 Jun;102(6):640-3.[3] Fleming M. et al. Educational and Health Outcomes of Children Treated for Attention-Deficit/Hyperactivity Disorder. JAMA Pediatr. 2017. May 1.[4] Borschuk AP. et al. The influence of comorbid asthma on the severity of symptoms in children with attention-deficit hyperactivity disorder. J Asthma. 2017 May 1:1-7.----------Chien WC, Chung CH, Lin FH, Yeh CB, Huang SY, Lu RB, Chang HA, Kao YC, Chiang WS, Chou YC, Tsao CH, Wu YF, & Tzeng NS (2017). The risk of injury in adults with attention-deficit hyperactivity disorder: A nationwide, matched-cohort, population-based study in Taiwan. Research in developmental disabilities, 65, 57-73 PMID: 28458048... Read more »

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I originally began writing this post in the last week of November 2016 following first sight of the study abstract by Anthony Mawson and colleagues [1] and their journey into a topic that has had its fair share of discussion/argument* (*delete as appropriate) with autism in mind down the years: are vaccines or immunisation patterns potentially linked to [some] autism?As it happened, this post was shelved for some time because (a) only an abstract appeared despite a publication date accompanying the initial open-access submission in a Frontiers journal and (b) the subsequent sudden disappearance of the abstract from the publishers website following some discussions on social media about the paper and the review process (see here and see here for more information).The study then appeared in a different journal (April 2017) before once again disappearing.Now it's back - for now - in the same journal, so once again it's fodder for this blog...As I always do when it comes to any chatter specifically on this topic, I should reiterate a few things: (a) the prime directive of this blog - no clinical or medical advice is given or intended - and (b) that vaccines save lives. I know some people attribute other factors to that 'life-saving' angle when it comes to vaccines over the longer term (better health, better environment, etc), but one really only needs to look at the protective effect of the various meningitis vaccines for example, to see their results in something like real-time. I repeat again: vaccines save lives.What however does seem to be missing from at least some of the general discussion about vaccines as a whole and their very positive health effects is the fact that they are medicines. As such they are not somehow impervious to potentially producing side-effects for some people, albeit a small proportion of people who use them. The problem at the moment is, that we don't really know everything there is to know about which people might be at greater risk of side-effects than others (although some clues are emerging) and importantly, how all those side-effects may manifest. Science - metabolomic science - is however starting to tackle some aspects of these issues [2] minus too much hype at the present time.As per the title of this post, Mawson et al set about examining whether there were differences between those children who were vaccinated and those un-vaccinated across "a broad range of health outcomes." In line with the previous history hypothesising about autism and specific vaccination, the authors focused on any 'association' between vaccination status and neurodevelopmental disorders (NDD) taking into account other potentially confounding variables.The source data for those vaccinated / un-vaccinated children participants (N=666) was an anonymous online questionnaire completed by mothers of children who were members of various homeschooling organisations in four regions of the United States. Homeschooling refers to a situation where a child is educated at home outside of the mainstream education system choices. Homeschoolers were selected for study because, according to the authors, a "higher proportion are unvaccinated compared to public school children."Results: around 40% of the participants were indeed described as un-vaccinated in the Mawson cohort. This is quite a bit higher than other estimates [3] specifically looking at homeschooled children. Then to some of the details: "Vaccinated children were significantly less likely than the unvaccinated to have been diagnosed with chickenpox and pertussis." If you needed more evidence that vaccines work, that last sentence kinda provides you with it, particularly in light of what diseases like pertussis can potentially do to the most vulnerable.And then some potential controversies: vaccinated children were significantly more likely to have been diagnosed with pneumonia, otitis media, allergies and NDDs (defined as autism spectrum disorder, attention deficit hyperactivity disorder, and/or a learning disability). After some statistical adjustment for potentially confounding variables, authors reported that "vaccination, nonwhite race, and male gender were significantly associated with NDD after controlling for other factors." I might also draw your attention to the reported finding that: "preterm birth and vaccination combined was strongly associated with NDD in the final adjusted model with interaction, more than doubling the odds of NDD compared to vaccination alone." This might suggest that there are synergistic variables at work influencing any identified risk continuing a research theme [4]. Indeed, the same authors have devoted a whole other article to this finding [5] (this paper also went through the same disappearing-reappearing act too).Wearing the objective blinkers of science, this is by no means perfect research. Not only are there potential issues related to the use of an on-line questionnaire (and anonymous at that), the focus on subjective reports over inspection of more objective medical records (even though parents were asked to obtain and use their child's vaccination record(s) when completing the questionnaire), and problems associated with recall (including possible telescoping effects), there are a whole host of other issues that one could cite in relation to such research and potential biases that could/might have influenced the results (including factors such as this one). I might also add that the Mawson study did not appear to 'name names' when it came to which individual vaccines may or may not have been involved in their findings despite asking questions about if and when specific immunisations were administered to participants. Indeed authors noted: "We did not set out to test a specific hypothesis about the association between vaccination and health." Then there is also the 'reaction' angle to papers such as this one to mention; bearing in mind that science these days does not exist in some sort of social/cultural vacuum as per other very recent and very relevant examples. Cumulatively, you can see that there ... Read more »

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I'm not a great fan of the term 'functioning' when it comes to autism (see here) hence the quote marks around high-functioning in the title of this post. Yes, I understand the message that it's trying to convey and that we don't have viable alternatives at the moment. It just however seems a little sweeping in terms of 'generalised' describing and labelling of people...No mind. Today I'd like to bring the paper by Özdem Ertürk Çetin and colleagues [1] to your attention and the observation that their results "support the fact that EEG abnormalities are observed at a higher rate also in ASD [autism spectrum disorder] with a better functionality." EEG - electroencephalographic or electroencephalogram - refers to the recording of electrical activity in the brain. Although in small amounts, our cells use electrical signals to message each other; said activity in the brain can be picked up and recorded using some rather sensitive equipment. EEGs are the method of choice when it comes to investigating epilepsy or related seizure disorders (such conditions are epitomised by abnormal electrical activity between cells).The connection between autism and epilepsy / seizure disorder is one that has persisted for many years (see here); even now to the point where research is starting to talk about autism / autistic traits being a feature of some cases of epilepsy (see here). Quite a bit of the research looking at autism and epilepsy has tended to suggest that epilepsy may be a little more over-represented for those towards the more severe end of the autism spectrum (i.e. in relation to presentation of symptoms and the presence of some degree of learning / intellectual disability). The Ertürk Çetin findings report that even in those with described 'better functionality' there may be disturbances in relation to the measurement of EEGs.Looking for "the presence of EEG abnormalities in sixteen children diagnosed with high-functioning ASD" researchers reported that whilst none of the participants had clinical seizures (the overt expression of epilepsy) "5 patients (31.3%) were detected to have EEG abnormalities." Bearing in mind the quite small participant numbers and the fact that no control groups (asymptomatic or otherwise) were included for comparisons, this is quite an important finding. I agree with the authors when they say that: "The potential impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy should be considered during long-term follow-up of these patients." In other words, whenever a diagnosis of autism or ASD is received, one should always consider the possibility that a heightened risk of epilepsy / seizure / abnormal EEG patterns might also be a feature of presentation irrespective of "functioning" status.----------[1] Ertürk Çetin Ö. et al. EEG abnormalities and long term seizure outcome in high functioning autism. Acta Neurol Belg. 2017 Apr 26.----------Ertürk Çetin Ö, Korkmaz B, Alev G, & Demirbilek V (2017). EEG abnormalities and long term seizure outcome in high functioning autism. Acta neurologica Belgica PMID: 28447214... Read more »

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A post recently published on the Spectrum website led to my blogging entry today, and the observation that: 'Alternative screen finds high autism prevalence in U.S. state'.Discussing results delivered at IMFAR 2017 the research in question was that presented by Laura Carpenter and colleagues [1] (someone with quite a track record in autism research). This was a conference presentation and seemingly not yet peer-reviewed publication, so one needs to be a little cautious about making big claims just yet. That being said, there have been research hints that these results would be forthcoming [2] around this time.The headline finding was that the prevalence of autism spectrum disorder (ASD) in one particular part of the United States for the birth year 2004 was probably quite a bit higher than that previously reported/estimated based on initial screening for possible ASD and then actual assessment. Details of the initiative used in this research - the South Carolina Children’s Educational Surveillance Study (SUCCESS) - can be found here.Some 4100 children were "screened for ASD using the Social Communication Questionnaire." Those who were deemed 'at risk' for autism and a small proportion of those not hitting those *might be autism* thresholds were asked back for a more detailed interview. Although the number of children actually followed-up and interviewed who were eligible for further assessment was not particularly great, the authors were able to draw up an estimated prevalence of autism based on those who did complete the study. The figure: "ASD prevalence in this sample is 3.62%" roughly equivalent to 1 in 28 children. I say this in the context that in the United States and elsewhere, autism rates and/or numbers of cases are still high (see here and see here) and acknowledgement of the implications of such increases when it comes to services such as education, healthcare and the like.The Spectrum article focuses quite a bit on the participation rate noted in the Carpenter study but another snippet of information is also included in the conference abstract that is worthy of discussion. A detail that reads: "Six children (6/52; 12%) had a clear developmental history of ASD but did not display clinically significant symptoms at the time of participation in this study." Further: "12% with a history of ASD no longer had significant ASD-related symptoms, providing further support for the potential for optimal outcomes in some individuals."I'm rather interested in that 12% figure with 'optimal outcome'. Optimal outcome describes cases where a clear indication/diagnosis of autism has been seen/received, but for whatever reason(s) diagnostic thresholds are not longer met at a future assessment point. I've covered this group quite a few times on this blog, most notably in relation to a previous estimate of 9% of those diagnosed with autism potentially falling into this category (see here). Appreciating that such data challenges the assumption that *all* autism is a lifelong condition (indeed, stretching across the entire autism spectrum - see here), I'd reiterate that those described as being 'optimal outcomers' represent an important subgroup on the autism spectrum in these days of plural autisms (see here). Not least is the question: Why? Why do these children not maintain their diagnosis and what lessons (if any) can be learned for the wider autism spectrum, particularly also in the context that various quite disabling comorbidities might also be 'reduced' alongside core autism symptoms in this group.We await formal peer-reviewed publication of the Carpenter findings and perhaps some further details.To close, upon introducing my brood to the music of Kate Bush, I am yet again reminded just how good a singer/performer she really is...----------[1] Carpenter LA. et al. The Prevalence of Autism Spectrum Disorder in School Aged Children: Population Based Screening and Direct Assessment. IMFAR 2017.[2] Carpenter LA. et al. Screening and direct assessment methodology to determine the prevalence of autism spectrum disorders. Ann Epidemiol. 2016 Jun;26(6):395-400.----------Carpenter LA, Boan AD, Wahlquist AE, Cohen A, Charles J, Jenner W, & Bradley CC (2016). Screening and direct assessment methodology to determine the prevalence of autism spectrum disorders. Annals of epidemiology, 26 (6), 395-400 PMID: 27230493... Read more »

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I don't want to spend too much time talking about yet another paper from the research tag-team that is Hornig & Lipkin [1] (open-access) on the topic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). But this latest addition to their research repertoire (see here) is deserving of several comments.Not least are the observations made by the authors - including one Brent Williams who some might remember from autism research history (see here) and Jose Montoya who has also made a mark in CFS/ME research circles (see here) - on how the collected wee beasties that inhabit our gastrointestinal (GI) tract might have some role to play when it comes to at least some cases of CFS/ME. Yes it's gut microbiome research time again.The press release accompanying the paper by Dorottya Nagy-Szakal and colleagues can be seen here. The long-and-short of it was that: "Independent of IBS [irritable bowel syndrome], ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity." Further: "Plasma cytokines did not define ME/CFS disease groups in our cohort." There could be some good reasons for that last sentence looking at immune-related molecules on the basis of other study results (see here) but further investigations are required.I have to say that outside of the observations that particular types of bacteria seem to be more or less prevalent in cases of CFS/ME (yet again) I was rather more interested in the finding that over 40% of the cohort also met criteria for IBS. I say that on the basis that I've already talked about 'abdominal discomfort syndrome' as a feature of some CFS/ME (see here) alongside findings that certain foods *might* also play a role in the bowel symptoms accompanying CFS/ME (see here).In these days of increasing pluralisation of spectrums (the autisms, the schizophrenias, etc) it is probably also quite useful to think about pluralising the diagnostic label CFS/ME too. Assuming we can get the diagnostic criteria right (see here) we could have a phenotype of CFS/ME that, for example, has a stronger bowel-related clinical signature than other forms. The further implications that the GI tract might play a role in CFS/ME in relation to either primary or secondary symptoms might also inform intervention. So, we kinda know that use of probiotics might be something to think about for some cases of IBS (see here). There is also some preliminary evidence that certain probiotics might also impact on some of the 'psychological' features (careful with that term) which can accompany CFS/ME [2]. The possibility of connections exist and therefore require further scientific exploration.----------[1] Nagy-Szakal D. et al. Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome. 2017; 5: 44.[2] Rao AV. et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.----------Nagy-Szakal D, Williams BL, Mishra N, Che X, Lee B, Bateman L, Klimas NG, Komaroff AL, Levine S, Montoya JG, Peterson DL, Ramanan D, Jain K, Eddy ML, Hornig M, & Lipkin WI (2017). Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 5 (1) PMID: 28441964... Read more »

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I was VERY happy to read the paper published by Erman Esnafoglu and colleagues [1] suggesting that: "zonulin, which regulates intestinal permeability, plays a role in the development of symptoms of ASD [autism spectrum disorder]."Zonulin - something that "can be used as a biomarker of impaired gut barrier function for several autoimmune, neurodegenerative, and tumoral diseases" [2] - is a compound that I've been interested in for a while on this and other blogs (see here). The primary reason for the interest is that connection to intestinal permeability and how 'leaky gut' may well show some relevance to some autism (see here and see here). The thing that was up-to-now missing from the research chatter about intestinal hyperpermeability and autism was the measurement of zonulin on the basis that elevated levels of zonulin show a connection to dietary elements such as gliadin (a facet of gluten) [3]. This is particularly relevant because previous data has observed a possible link between use of a gluten-free diet and a reduction in intestinal permeability in relation to autism [4]. All this is [peer-reviewed] research music to my ears (see here)...Esnafoglu et al set about measuring serum levels of zonulin in 32 participants diagnosed with an autism spectrum disorder (ASD) compared with 33 not-autism controls. Yet again, the words 'healthy controls' are used by the authors to define the control group and yet again, the assumption is that those participants with autism are somehow 'unhealthy'. Researchers, please just call it what it is: not-autism controls (the term 'neurotypical' also tells us nothing about control groups either). Measurement of zonulin was via ELISA (enzyme-linked immunosorbent assay) and researchers also threw in a measure of autism severity based on use of the Childhood Autism Rating Scale (CARS).Results: well, the results seemed to be in the expected direction: "Serum zonulin levels were significantly higher in the patients with ASD (122.3 ± 98.46 ng/mL) compared with the healthy controls (41.89 ± 45.83 ng/mL)." Authors also identified a fairly healthy correlation between the CARS score and zonulin levels. These results imply that issues with intestinal permeability - leaky gut - seem to be present in relation to at least some autism. A shocker, I know.Obviously there is more research to do in this area; not least to increase the sample size, look at dietary intake/status as a function of zonulin measurement and explore the possibility that the genetics of zonulin production might also be *involved* in some autism [5]. I might add that other research on zonulin in relation to diagnoses not necessarily uncommon to autism might also be revealing (see here).Insofar as what to do about elevations in zonulin as and when detected in cases of autism, well the dietary link to zonulin production implies that the horror that is a gluten-free (GF) diet might be something to consider. The suggestion of a 'bacterial link' to zonulin production also suggests another possible intervention target in these days of gut microbiomes and autism (see here) although I think we have to be slightly careful about the use of some preparations. There is also another avenue for research speculation based on the development of zonulin (receptor) inhibitors such as Larazotide acetate [6] (otherwise known as AT-1001). With no medical or clinical advice given or intended, the evidence base for this zonulin-affecting compound is looking promising [7] with much more to come...In conclusion, zonulin has arrived on the autism research scene, and I'm expecting to see more peer-reviewed science on this topic in future times. Intestinal hyperpermeability, diet and [some] autism looks to be squarely back on the research agenda.----------[1] Esnafoglu E. et al. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects. J Pediatrics. 2017. May 11.[2] Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Annals of the New York Academy of Sciences. 2012; 1258(1) :25-33.[3] Lammers KM. et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008 Jul;135(1):194-204.e3.[4] de Magistris L. et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418-24.[5] Tripathi A. et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16799-804.[6] Fasano A. Intestinal Permeability and its Regulation by Zonulin: Diagnostic and Therapeutic Implications. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2012;10(10):1096-1100.[7] Leffler DA. et al. Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial. Gastroenterology. 2015; 148: 1311-1319.----------Esnafoglu, E., Cırrık, S., Ayyıldız, S., Erdil, A., Ertürk, E., Daglı, A., & Noyan, T. (2017). Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects The Journal of Pediatrics DOI: 10.1016/j.jpeds.2017.04.004... Read more »

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Nootropic, defined as a 'smart drug' or cognitive enhancer, is generally taken to mean a substance/compound/medicine that has some positive effect(s) on aspects of cognition. I've talked about the possibility that various compounds might fit this bill on this blog (see here for example) but today I'm discussing another quite important potential nootropic: exercise.It was the paper by Joseph Michael Northery and colleagues [1] (open-access) that added exercise to the nootropic categorisation on the premise of their meta-analysis results suggesting that "physical exercise interventions are effective in improving cognitive function in adults aged >50 years, regardless of cognitive status." As you can imagine, findings such as that tend to generate news headlines as per this one.Including the results of some 39 studies where exercise and cognition were included as watchwords and trials were of the randomised-controlled design, researchers set about analysing the collected data covering various types of exercise and various cognitive outcomes. Aside from some issues with various forms of bias, most prominently with regards to blinding(!), they concluded that various types of exercise seemed to positively impact on cognitive functions. Particularly notable were the positive effects on executive functions: "a set of cognitive processes responsible for the initiation and monitoring of goal-orientated behaviours" and aspects of memory via the use of resistance training (i.e. using weights). Other more aerobic exercise regimes also seemed to have positive effects on other aspects of cognition too. It seems some combination of aerobic and resistance exercise regimes might provide the best generalised advice according to the authors "of at least moderate intensity and at least 45 min per session, on as many days of the week as possible." Just going back to that resistance training - executive functioning link being proposed, I wonder whether there may be other investigations to be carried out here with specific labels in mind [2].Added to other research talking about 'exercise as medicine' (see here) and more particularly that exercise *might* have some important effects for aspects of psychological health and wellbeing (see here and see here for examples) there is a peer-reviewed, evidence-based picture emerging. It suggests that messages about moving more (see here) as being important for weight and BMI might be only the tip of iceberg.And although not for everyone, I'm minded to yet again extol the virtues of the martial arts which also might have some "positive effect on some aspects of cognition" [3] (even for those under 50 years old with middle-aged hips like mine)...----------[1] Northey JM. et al. Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis. Br J Sports Med. 2017. April 24.[2] Demetriou EA. et al. Autism spectrum disorders: a meta-analysis of executive function. Molecular Psychiatry. 2017. April 25.[3] Fabio RA. & Towey GE. Cognitive and personality factors in the regular practice of martial arts. J Sports Med Phys Fitness. 2017 May 5.----------Northey, J., Cherbuin, N., Pumpa, K., Smee, D., & Rattray, B. (2017). Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis British Journal of Sports Medicine DOI: 10.1136/bjsports-2016-096587... Read more »

Why is this post inappropriate?

The question posed in the title of this post 'Could an "ill-state" associated with anorexia nervosa mimic the symptoms of autism?' stems from the findings reported by Heather Westwood and colleagues [1] (open-access).They continued a research theme looking at the potential 'overlap' when it comes to autism and eating disorders such as anorexia nervosa (AN) (see here). Notably, researchers questioned whether the finding that some 50% of their cohort "scored above the clinical cut-off on the ADOS-2" but "when developmental history was obtained, only 10% met diagnostic criteria for ASD [autism spectrum disorder]" could be due to "the ill-state associated with AN."The Westwood paper is open-access so doesn't need any further grand explanations from me. The research caveats alongside relying on quite a small cohort - "40 females aged between 12 and 18" - were that this was a snapshot study not a longitudinal one and whilst relying on data other than that just linked to the presence of autism traits, they did not control for things like social anxiety "which could lead to high scores on the ADOS-2." Interesting.On the question of whether 'active AN' (please pardon my lack of knowledge on this topic) might have the ability to 'provoke' autistic traits, I have to say that I'm quite intrigued. This might have a few, quite important, implications not least that (a) autistic traits can be 'acquired' as per what has been noted under other different circumstances (see here and see here for examples) and (b) the potential stability of said traits might not be particularly stable for everyone at every time (see here). On that last point, we do need a lot more data as to what happens/happened when AN is treated/managed or goes into remission for example and any subsequent impact on autistic traits.It's too early to start talking mechanisms when it comes to AN and autistic traits in light of this data alone. I might also venture into the idea that other comorbidities than can appear alongside AN might also have some impact on clinical presentation (see here) and are also in need to further investigation in the context of any eating disorders - autism correlation. Indeed, there are potentially lots of variables that need to be kept in mind (see here and see here) before any sweeping generalisation are made...----------[1] Westwood H. et al. Assessing ASD in Adolescent Females with Anorexia Nervosa using Clinical and Developmental Measures: a Preliminary Investigation. J Abnorm Child Psychol. 2017 Apr 17.----------Westwood, H., Mandy, W., Simic, M., & Tchanturia, K. (2017). Assessing ASD in Adolescent Females with Anorexia Nervosa using Clinical and Developmental Measures: a Preliminary Investigation Journal of Abnormal Child Psychology DOI: 10.1007/s10802-017-0301-x... Read more »

Why is this post inappropriate?

I tread carefully when discussing the results published by Ragini Heeramun and colleagues [1] on the topic of "whether autism is associated with convictions for violent crimes" and "the associated risk and protective factors." Carefully because, as I've indicated on other occasions (see here), people commit crimes not labels, and sweeping generalisations about labels, specific types of crime and/or the concept of 'dangerousness' tend to do very little to help anyone in the long term.Still, I do think it is important that issues such as offending in the context of autism spectrum disorder (ASD) are not brushed under the carpet. I say this bearing in mind that a few high profile cases where autism has been mentioned alongside have been highlighted in the media recently here in Blighty (see here and see here). Indeed, in these days of cyber-terrorism linked to extremism for example, I'd like to see quite a bit more scientific investigation into the ways of protecting those on the autism spectrum from being lured into such activities alongside studies on the possible hows-and-whys of people entering into such behaviours.Heeramun et al relied on data from the Stockholm Youth Cohort where some 5,700 participants had a recorded ASD diagnosis. Data was cross-referenced with that from the Swedish National Crime Register to ascertain how many people were charged with offences where violence was a factor. Comparing those with autism with those with not-autism, researchers concluded that: "Individuals with autism, particularly those without intellectual disability, initially appeared to have a higher risk of violent offending." They do temper that finding with the observation that "these associations markedly attenuated after co-occurring attention-deficit/hyperactivity disorder (ADHD) or conduct disorder were taken into account" suggesting that comorbidity might count. Indeed, this data tallies with other independent findings suggesting that a range of 'adverse' life events can be a significant feature of ADHD and conduct disorder in the long-term (see here) and for example, that autism and ADHD in the prison population should considered (see here).Alongside, authors talked about how various other factors might also influence risk of violent offending ("parental criminal and psychiatric history and socioeconomic characteristics") and importantly, how: "Better school performance and intellectual disability appeared to be protective." That intellectual (learning) disability accompanying autism seems to be protective against conviction for a violent crime with autism in mind is probably due in part to the increased supervision given to such individuals. This is a point that has been raised in previous peer-reviewed research too (see here).The take-away messages are once again, sweeping generalisations about all autism being *linked to* violent crime are not needed and that comorbidity might count (as it seems to on many occasions) when it comes to variables being linked to autism (see here for another example). As with such crime in the general population, there are a myriad of often quite individual factors contributing to such behaviours, but alongside: "Better understanding and management of comorbid psychopathology in autism may potentially help preventive action against offending behaviors in people with autism."----------[1] Heeramun R. et al. Autism and Convictions for Violent Crimes: Population-Based Cohort Study in Sweden. JAACAP. 2017. April 3.----------Heeramun, R., Magnusson, C., Gumpert, C., Granath, S., Lundberg, M., Dalman, C., & Rai, D. (2017). Autism and Convictions for Violent Crimes: Population-Based Cohort Study in Sweden Journal of the American Academy of Child & Adolescent Psychiatry DOI: 10.1016/j.jaac.2017.03.011... Read more »

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